A major advance in the treatment of HIV-infected patients has been the use of potent combinations of antiretroviral drugs (highly active antiretroviral therapy, or "HAART"). These drugs have led to improved survival and decreased morbidity in those patients able to obtain these drugs and adhere to complex treatment regimens. Unfortunately, an increasingly large subset of patients either do not initially repond to HARRT, or initially respond and then fail based on virologic and immunologic parameters (ie, increasing HIV RNA [viral load] or decreasing CD4 cell count). To date, the "holy grail" of antiretroviral therapy has been achieving suppression of plasma HIV RNA to undetectable levels; however, clinicians have recently noted a dissociation between continued clinical and immunologic benefits of HAART and "failure" of HARRT as measured by imcomplete supression of HIV RNA. We hypothesize that heavily pretreated patients continue to derive clinical, immunologic, and nutritional benefits despite failing HAART based on virologic criteria. We will test this hypothesis by carrying out a randomized clinical trial in 160 patients who have failed at least 2 previous regimens of HAART and have HIV RNA in plasma between 5,000 and 80,000 copies/ml, but stable clinical status and CD4 cell counts over the preceding 6 months. 80 patients will be randomized to switch HAART regimen and 80 patients will continue their current regimen. Patients will be followed for 1 year and differences between the groups in clinical events, plasma HIV RNA, CD4 cell count, nutrition, and health-related quality of life will be determined. We will also measure HIV genotypic resistance, syncytium-inducing phenotype, and plasma protease inhibitor concentrations to determine the relationships to treatment failure and other outcome measures. The long-term objective of this proposal is to provide data that will help guide clinician decisions concerning changes of therapy for heavily pretreated patients with detectable viral load, but clinical stable and immunologic status.